Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia.

Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia.
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可注射电纺纤维-水凝胶复合材料顺序释放可乐定和罗哌卡因,用于长时间和步行局部镇痛

DOI:
10.7150/thno.74845
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发表时间:
2022
期刊:
影响因子:
12.4
通讯作者:
Hei, Ziqing
Hei, Ziqing
中科院分区:
医学1区
文献类型:
--
作者:
Chen, Sufang;Yao, Weifeng;Wang, Haixia;Wang, Tienan;Xiao, Xue;Sun, Guoliang;Yang, Jing;Guan, Yu;Zhang, Zhen;Xia, Zhengyuan;Li, Mingqiang;Tao, Yu;Hei, Ziqing

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理由:周围神经阻滞是传统的围手术期镇痛方法,具有镇痛效果好、全身毒性低的优点。然而,单次低剂量的局部麻醉剂仅提供几个小时的镇痛,并且高剂量导致不可逆的毒性,而持续输注麻醉剂是昂贵且复杂的。因此,有必要研制一种长效的、具有感觉选择性的局麻药用于安全的围手术期镇痛。研究方法:开发了一种可注射的复合材料,该复合材料包含负载罗哌卡因的聚(ε-己内酯)电纺纤维和负载可乐定的F127水凝胶(Fiber-Rop/Gel-Clo复合材料),用于仅用一次剂量的长效和行走区域镇痛。在大鼠坐骨神经阻滞模型中评价复合物的周围神经阻滞效果。并对复合材料的生物降解性和生物安全性进行了评价。结果如下:从水凝胶中优先释放的Clo迅速收缩外周动脉血管,减少Rop的血液吸收,从而增强注射部位的局部Rop积聚。随后从纤维中持续释放Rop,显著延长大鼠坐骨神经阻滞。值得注意的是,实现了惊人的感觉运动隔离效果,因为感觉阻滞(32.0 ± 1.4 h)持续时间显著长于运动阻滞(20.3 ± 0.9 h)。此外,Fiber-Rop/Gel-Clo复合材料在体内表现出良好的生物降解性和生物安全性。结论:我们设计的Fiber-Rop/Gel-Clo复合材料具有微创、持久的协同镇痛作用和显著的感觉运动隔离效应,为临床治疗区域性长期行走镇痛展示了良好的前景。
Rationale: Peripheral nerve block is a traditional perioperative analgesic method for its precise pain control and low systemic toxicity. However, a single low dose of local anesthetic merely provides a few hours of analgesia, and high dose results in irreversible toxicity, whereas continuous infusion of anesthetics is expensive and complicated. Therefore, it is necessary to develop a long-acting and sensory-selective local anesthetic for safe perioperative analgesia. Methods: An injectable composite comprising ropivacaine-loaded poly (ε-caprolactone) electrospun fiber and clonidine-loaded F127 hydrogel (Fiber-Rop/Gel-Clo composite) was developed for long-acting and walking regional analgesia with barely one dose. The peripheral nerve blockade effect of the composite was evaluated in a rat sciatic nerve block model. Also, the biodegradability and biosafety of the composite was evaluated. Results: The preferentially released Clo from the hydrogel rapidly constricted the peripheral arterial vessels, reducing the blood absorption of Rop and thus enhancing the local Rop accumulation at the injection site. The subsequently sustainable release of Rop from the fiber, significantly prolonged the sciatic nerve block of rats. Remarkably, an amazing sensorimotor segregation effect was achieved, as the sensory blockade (32.0 ± 1.4 h) lasted significantly longer than the motor blockade (20.3 ± 0.9 h). Additionally, the Fiber-Rop/Gel-Clo composite presented good biodegradability and biosafety in vivo. Conclusions: Our designed Fiber-Rop/Gel-Clo composite with minimal invasion, prolonged synergistic analgesia, and strikingly sensorimotor segregation effect, posted a promising prospect for regional long-term walking analgesia in clinical treatment.
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